The first proof that vaccines based on dendritic cells work.

Rays of hope: Scientists have shown that dendritic cell vaccines can help cancer patients live longer. Credit: Courtesy: David Hunt & U Wash-Cell Systems Initiative

An experimental cancer vaccine has for the first time been shown to significantly extend the lives of men with prostate cancer, Seattle-based Dendreon announced in February. The vaccine, Provenge, is based on dendritic cells, which help the immune system recognize tumors.

“If these results are true, this represents the first proof of principle of a dendritic [cell] vaccine altering the natural history of a solid tumor,” says Philip Kantoff, chief of solid tumor oncology at the Dana-Farber Cancer Institute in Boston, who was not involved with the study.

Cancer vaccines vary widely: they may employ whole proteins, tumor antigens, dendritic cells, killed tumor cells or tumor lysates. The goal of the vaccines is to prime the patient's immune system to recognize and destroy the tumor without harming normal cells.

Provenge carries the patients' own dendritic cells engineered to express a protein found on about 95% of prostate cancer cells. It is one of more than 15 vaccines in trials for a range of cancers, including lymphoma, melanoma, breast, lung and colorectal cancers, but the first to increase lifespan in advanced cancer patients.

For years cancer vaccines have been dogged by questions and controversy (Nat. Med. 10, 3; 2004). One ongoing concern is a lack of standardized vaccine production methods, says Nina Bhardwaj, director of the tumor vaccine program at New York University School of Medicine.

There are also questions about which cells and antigens to use in vaccines and the mode and frequency with which they should be administered. For example, mature dendritic cell vaccines seem to produce the best immune response when given either subcutaneously or intradermally, but not intravenously (Blood 10, 2235–2246; 2004). Researchers are also trying to determine whether vaccines will be need to be designed for specific cancers, or whether a universal vaccine could produce a robust immune response.

The Provenge trial has raised several questions of its own: 34% of men given Provenge, compared with 11% on placebo, were alive three years on, and lived 4.5 months on average longer. But paradoxically, the vaccine does not delay 'time to progression,' a measure of efficacy used in most cancer trials to denote the time before a tumor begins growing again, and Dendreon's primary endpoint in this trial.

We were all somewhat pleasantly surprised that Provenge showed a survival benefit., director . E. Roy Berger, Prostate Cancer Consultation and Treatment Service

“Because of this, we were all somewhat pleasantly surprised that Provenge showed a survival benefit,” says E. Roy Berger, director of the Prostate Cancer Consultation and Treatment Service in East Setauket, New York.

The vaccine only benefited a subgroup of men at earlier stages of the disease in a previous shorter trial, but even men with aggressive disease lived longer in this trial. One reason for that discrepancy may be that immunotherapy does not work as quickly as chemotherapy, which has a direct, cytotoxic effect, says Berger. “Cancer vaccines prime the immune system to attack cancer, a slower, more indirect process,” he says. This may mean that survival, and not time to progression, is a better measure of efficacy for cancer vaccines, Berger suggests.